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|Title: ||The pre-B-cell receptor associated protein VpreB3 is a useful diagnostic marker to identify c-MYC translocated lymphomas|
|Authors: ||Rodig, Scot J.|
Kutok, Jeffery L.
Paterson, Jennifer C.
Tumwine, Lynette K.
Johnson, Nathalie A.
Shipp, Margaret A.
Piris, Miguel A.
Grogan, Thomas M.
Pileri, Stefano A.
Gascoyne, Randy D.
|Issue Date: ||2010 |
|Publisher: ||Pensiero Scientifico / Ferrata Storti Foundation|
|Citation: ||Haematologica, 2010 95:xxx|
|Abstract: ||Background: During B-cell development, precursor B-cells transiently express the pre-B-cell receptor composed of μ heavy chain complexed with VpreB and λ5 surrogate light chain polypeptides. Recent profiling studies unexpectedly revealed abundant transcripts of one member of the VpreB family, VpreB3, in a subset of mature B-cells and Burkitt lymphoma.
Design and Methods: Here, we used a novel antibody to investigate the normal expression
pattern of VpreB3 protein in human hematolymphoid tissues, and determine whether VpreB3 can serve as a useful diagnostic biomarker for select B-cell lymphomas.
Results: We found that VpreB3 protein is normally expressed by precursor B-cells in bone marrow and by a subset of normal germinal center B-cells in secondary lymphoid organs. Among lymphoid malignancies, we found an association between VpreB3 expression and Bcell
tumors with c-MYC abnormalities. VpreB3 was highly expressed in all cases of Burkitt
lymphoma, whether of endemic or sporadic origin (44/44 cases, 100%), all cases of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (intermediate DLBCL/BL, 5/5 cases, 100%), and the majority of DLBCLs harboring a c-MYC translocation (15/18 cases, 83%). The expression of VpreB3 in DLBCLs without a c-MYC translocation was associated with c-MYC polysomy in 25/75 cases
(33%) but only rarely observed in DLBCLs lacking a c-MYC abnormality (9/98 cases, 9%).
Conclusions. We conclude that for B-cell tumors with features suggesting a possible c-MYC translocation, such as intermediate to large cell size and high proliferation rate, the presence of VpreB3 should prompt subsequent confirmatory genetic testing, whereas the absence of VpreB3 is virtually always associated with wildtype c-MYC alleles.|
|Description: ||Haematologica 2010 [Epub ahead of print]. This is an early release paper, published ahead of print on September 7, 2010 as doi:10.3324/haematol.2010.025767. Copyright 2010 Ferrata Storti Foundations.|
|Appears in Collections:||Research Articles (Health-Sciences)|
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